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Co-inhibition of glutaminolysis and one-carbon metabolism promotes ROS accumulation leading to enhancement of chemotherapeutic efficacy in anaplastic thyroid cancer
DC Field | Value | Language |
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dc.contributor.author | 김석모 | - |
dc.contributor.author | 윤혁준 | - |
dc.contributor.author | 이해경 | - |
dc.contributor.author | 장항석 | - |
dc.contributor.author | 황성순 | - |
dc.date.accessioned | 2023-10-19T05:50:24Z | - |
dc.date.available | 2023-10-19T05:50:24Z | - |
dc.date.issued | 2023-08 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/196292 | - |
dc.description.abstract | Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors with an extremely poor prognosis. Based on the several biological features related to glutamine metabolism in ATC, we hypothesized glutaminolysis inhibition induces cell death in ATC cells. However, glutamine metabolism inhibition triggered cell growth arrest independent of cell death in ATC, suggesting that other signaling pathways avoid glutamine metabolism inhibition-induced stress exist. To investigate the functional mechanism against glutamine metabolism inhibition, we conducted mRNA and ATAC-Sequencing data analysis and found that glutamine deprivation increased ATF4-mediated one-carbon metabolism. When we inhibited PHGDH, the first rate-limiting enzyme for one-carbon metabolism, cell growth arrest was promoted upon glutamine metabolism inhibition by accumulating intracellular ROS. We next observed that the co-inhibition of glutamine and one-carbon metabolism could augment the anticancer effects of drugs used in patients with ATC. Finally, single-cell RNA sequencing analysis revealed that one-carbon metabolism was strengthened through the evolutionary process from PTC to ATC. Collectively, our data demonstrate that one-carbon metabolism has a potential role of modulation of cell fate in metabolic stress and can be a therapeutic target for enhancing antitumor effects in ATC. © 2023. The Author(s). | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Nature Pub. Group | - |
dc.relation.isPartOf | CELL DEATH & DISEASE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Carbon | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Glutamine | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Reactive Oxygen Species | - |
dc.subject.MESH | Thyroid Carcinoma, Anaplastic* / drug therapy | - |
dc.subject.MESH | Thyroid Carcinoma, Anaplastic* / genetics | - |
dc.subject.MESH | Thyroid Carcinoma, Anaplastic* / metabolism | - |
dc.subject.MESH | Thyroid Neoplasms* / drug therapy | - |
dc.subject.MESH | Thyroid Neoplasms* / genetics | - |
dc.subject.MESH | Thyroid Neoplasms* / metabolism | - |
dc.title | Co-inhibition of glutaminolysis and one-carbon metabolism promotes ROS accumulation leading to enhancement of chemotherapeutic efficacy in anaplastic thyroid cancer | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Surgery (외과학교실) | - |
dc.contributor.googleauthor | Yeseong Hwang | - |
dc.contributor.googleauthor | Hyeok Jun Yun | - |
dc.contributor.googleauthor | Jae Woong Jeong | - |
dc.contributor.googleauthor | Minki Kim | - |
dc.contributor.googleauthor | Seyeon Joo | - |
dc.contributor.googleauthor | Hae-Kyung Lee | - |
dc.contributor.googleauthor | Hang-Seok Chang | - |
dc.contributor.googleauthor | Seok-Mo Kim | - |
dc.contributor.googleauthor | Sungsoon Fang | - |
dc.identifier.doi | 10.1038/s41419-023-06041-2 | - |
dc.contributor.localId | A00542 | - |
dc.contributor.localId | A06022 | - |
dc.contributor.localId | A05936 | - |
dc.contributor.localId | A03488 | - |
dc.contributor.localId | A05443 | - |
dc.relation.journalcode | J00482 | - |
dc.identifier.eissn | 2041-4889 | - |
dc.identifier.pmid | 37573361 | - |
dc.contributor.alternativeName | Kim, Seok Mo | - |
dc.contributor.affiliatedAuthor | 김석모 | - |
dc.contributor.affiliatedAuthor | 윤혁준 | - |
dc.contributor.affiliatedAuthor | 이해경 | - |
dc.contributor.affiliatedAuthor | 장항석 | - |
dc.contributor.affiliatedAuthor | 황성순 | - |
dc.citation.volume | 14 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 515 | - |
dc.identifier.bibliographicCitation | CELL DEATH & DISEASE, Vol.14(8) : 515, 2023-08 | - |
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